While FDA approved drugs are approved as safe and effective for the population as a whole, the majority of drugs do not work in all patients to which they are administered. However at present, many drugs are administered to patients without a prediction of whether or not the drug will be effective in a particular patient. This results in higher than necessary health care costs and risk to patients. There is a need in the art to develop new patient selection methods that will match patients to the correct treatment.
It has been known that one of the most common types of genetic alterations in cancer is the loss-of-function mutations in tumor-suppressor genes. The DPC4 gene (Deleted in Pancreatic Cancer locus 4), a tumor-suppressor gene located at 18q21.1, has been shown to mediate the effects of TGF-superfamily signaling, resulting in downstream growth inhibition. However, DPC4 is inactivated in approximately 55% of pancreatic adenocarcinomas. Pancreatic cancer is the fifth most common cause of tumor-related deaths in the industrialized world. Fewer than 10% to 20% of patients are candidates for surgery at the time of presentation, and <20% of patients who undergo curative resection are alive after 5 years. Despite recent progress, there is no modality for early detection of pancreatic cancer. In addition, mutations in DPC4 also have been identified in other tumor types, including bladder (12-35%), lung (24-65%), prostate (19-45%), ovarian (27-67%) carcinomas, 10% of proximal and 55% of distal bile duct carcinomas. Therefore there is a need to identify potential lethal targets against the deficiency of the DPC4 gene, so that the lethal targets may be used for developing treatments for cancers, particularly for cancers with inactivated DPC4 gene or gene product.